Department of Biotechnology
inStem (Institute for Stem Cell Science and Regenerative Medicine)

Polymeric micelles effectively reprogram the tumor microenvironment to potentiate nano-immunotherapy in mouse breast cancer models.

Publication Type

Journal Article

Date of Publication

November 22, 2022

Journal

Nature communications

Volume/Issue

13/1

ISSN

2041-1723

Nano-immunotherapy improves breast cancer outcomes but not all patients respond and none are cured. To improve efficacy, research focuses on drugs that reprogram cancer-associated fibroblasts (CAFs) to improve therapeutic delivery and immunostimulation. These drugs, however, have a narrow therapeutic window and cause adverse effects. Developing strategies that increase CAF-reprogramming while limiting adverse effects is urgent. Here, taking advantage of the CAF-reprogramming capabilities of tranilast, we developed tranilast-loaded micelles. Strikingly, a 100-fold reduced dose of tranilast-micelles induces superior reprogramming compared to free drug owing to enhanced intratumoral accumulation and cancer-associated fibroblast uptake. Combination of tranilast-micelles and epirubicin-micelles or Doxil with immunotherapy increases T-cell infiltration, resulting in cures and immunological memory in mice bearing immunotherapy-resistant breast cancer. Furthermore, shear wave elastography (SWE) is able to monitor reduced tumor stiffness caused by tranilast-micelles and predict response to nano-immunotherapy. Micellar encapsulation is a promising strategy for TME-reprogramming and SWE is a potential biomarker of response.

Alternate Journal

Nat Commun

PubMed ID

36418896

PubMed Central ID

PMC9684407

Authors

Myrofora Panagi
Fotios Mpekris
Pengwen Chen
Chrysovalantis Voutouri
Yasuhiro Nakagawa
John D Martin
Tetsuro Hiroi
Hiroko Hashimoto
Philippos Demetriou
Chryso Pierides
Rekha Samuel
Andreas Stylianou
Christina Michael
Shigeto Fukushima
Paraskevi Georgiou
Panagiotis Papageorgis
Petri Ch Papaphilippou
Laura Koumas
Paul Costeas
Genichiro Ishii
Motohiro Kojima
Kazunori Kataoka
Horacio Cabral
Triantafyllos Stylianopoulos

Keywords

Neoplasms
Animals
Mice
Polymers
Micelles
Tumor Microenvironment
Immunotherapy
ortho-Aminobenzoates
Immunologic Factors
Drug-Related Side Effects and Adverse Reactions